Thinner inner retinal layers are associated with lower cognitive performance, lower brain volume, and altered white matter network structure-The Maastricht Study.

INTRODUCTION: The retina may provide non-invasive, scalable biomarkers for monitoring cerebral neurodegeneration. METHODS: We used cross-sectional data from The Maastricht study (n = 3436; mean age 59.3 years; 48% men; and 21% with type 2 diabetes [the latter oversampled by design]). We evaluated associations of retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses with cognitive performance and magnetic resonance imaging indices (global grey and white matter volume, hippocampal volume, whole brain node degree, global efficiency, clustering coefficient, and local efficiency). RESULTS: After adjustment, lower thicknesses of most inner retinal layers were significantly associated with worse cognitive performance, lower grey and white matter volume, lower hippocampal volume, and worse brain white matter network structure assessed from lower whole brain node degree, lower global efficiency, higher clustering coefficient, and higher local efficiency. DISCUSSION: The retina may provide biomarkers that are informative of cerebral neurodegenerative changes in the pathobiology of dementia.

Alcohol consumption and microvascular dysfunction: a J-shaped association: The Maastricht Study.

BACKGROUND: Microvascular dysfunction (MVD) is an important contributor to major clinical disease such as stroke, dementia, depression, retinopathy, and chronic kidney disease. Alcohol consumption may be a determinant of MVD. OBJECTIVE: Main objectives were (1) to study whether alcohol consumption was associated with MVD as assessed in the brain, retina, skin, kidney and in the blood; and (2) to investigate whether associations differed by history of cardiovascular disease or sex. DESIGN: We used cross-sectional data from The Maastricht Study (N = 3,120 participants, 50.9% men, mean age 60 years, and 27.5% with type 2 diabetes [the latter oversampled by design]). We used regression analyses to study the association between total alcohol (per unit and in the categories, i.e. none, light, moderate, high) and MVD, where all measures of MVD were combined into a total MVD composite score (expressed in SD). We adjusted all associations for potential confounders; and tested for interaction by sex, and history of cardiovascular disease. Additionally we tested for interaction with glucose metabolism status. RESULTS: The association between total alcohol consumption and MVD was non-linear, i.e. J-shaped. Moderate versus light total alcohol consumption was significantly associated with less MVD, after full adjustment (beta [95% confidence interval], -0.10 [-0.19; -0.01]). The shape of the curve differed with sex (Pinteraction = 0.03), history of cardiovascular disease (Pinteraction < 0.001), and glucose metabolism status (Pinteraction = 0.02). CONCLUSIONS: The present cross-sectional, population-based study found evidence that alcohol consumption may have an effect on MVD. Hence, although increasing alcohol consumption cannot be recommended as a policy, this study suggests that prevention of MVD may be possible through dietary interventions.

A 4-Week Diet Low or High in Advanced Glycation Endproducts Has Limited Impact on Gut Microbial Composition in Abdominally Obese Individuals: The deAGEing Trial.

Dietary advanced glycation endproducts (AGEs), abundantly present in Westernized diets, are linked to negative health outcomes, but their impact on the gut microbiota has not yet been well investigated in humans. We investigated the effects of a 4-week isocaloric and macronutrient-matched diet low or high in AGEs on the gut microbial composition of 70 abdominally obese individuals in a double-blind parallel-design randomized controlled trial (NCT03866343). Additionally, we investigated the cross-sectional associations between the habitual intake of dietary dicarbonyls, reactive precursors to AGEs, and the gut microbial composition, as assessed by 16S rRNA amplicon-based sequencing. Despite a marked percentage difference in AGE intake, we observed no differences in microbial richness and the general community structure. Only the Anaerostipes spp. had a relative abundance >0.5% and showed differential abundance (0.5 versus 1.11%; p = 0.028, after low- or high-AGE diet, respectively). While the habitual intake of dicarbonyls was not associated with microbial richness or a general community structure, the intake of 3-deoxyglucosone was especially associated with an abundance of several genera. Thus, a 4-week diet low or high in AGEs has a limited impact on the gut microbial composition of abdominally obese humans, paralleling its previously observed limited biological consequences. The effects of dietary dicarbonyls on the gut microbiota composition deserve further investigation.

Intrahepatic lipid content is independently associated with soluble E-selectin levels: The Maastricht study.

BACKGROUND: Evidence is accumulating that liver sinusoidal endothelial cells are involved in the pathogenesis of non-alcoholic fatty liver disease. Previous studies have suggested that the endothelial biomarker soluble E-selectin (sE-selectin) is to an important extent liver-derived. AIMS: To study the relationship of intrahepatic lipid (IHL) content with sE-selectin at the population level. METHODS: This study was conducted in participants of The Maastricht Study (n = 1,634), a population-based cohort study enriched with patients with type 2 diabetes. We assessed the cross-sectional association between IHL content, quantified by MRI, and sE-selectin via multivariable regression with adjustment for age, sex, type 2 diabetes, educational level, BMI, Dutch Healthy Diet index, physical activity, and the Matsuda index. RESULTS: Standardized IHL content was associated with (log) sE-selectin (age-, sex- and type 2 diabetes-adjusted regression coefficient [B]: 0.048 [95%CI:0.038;0.058], p<0.001), even after full adjustment (B: 0.030 [0.019;0.042], p<0.001). Such an association was not observed for soluble vascular cell adhesion molecule 1 (sVCAM-1) levels. CONCLUSION: IHL content is an independent determinant of sE-selectin at the population level. These findings support further studies to unravel the involvement of liver sinusoidal endothelial cells in the different stages of non-alcoholic fatty liver disease and the specific role of E-selectin herein.

Fructose Intake From Fruit Juice and Sugar-Sweetened Beverages Is Associated With Higher Intrahepatic Lipid Content: The Maastricht Study.

OBJECTIVE: Epidemiological evidence regarding the relationship between fructose intake and intrahepatic lipid (IHL) content is inconclusive. We, therefore, assessed the relationship between different sources of fructose and IHL at the population level. RESEARCH DESIGN AND METHODS: We used cross-sectional data from The Maastricht Study, a population-based cohort study (n = 3,981; mean ± SD age: 60 ± 9 years; 50% women). We assessed the relationship between fructose intake (assessed with a food-frequency questionnaire)-total and derived from fruit, fruit juice, and sugar-sweetened beverages (SSB)-and IHL (quantified with 3T Dixon MRI) with adjustment for age, sex, type 2 diabetes, education, smoking status, physical activity, and intakes of total energy, alcohol, saturated fat, protein, vitamin E, and dietary fiber. RESULTS: Energy-adjusted total fructose intake and energy-adjusted fructose from fruit were not associated with IHL in the fully adjusted models (P = 0.647 and P = 0.767). In contrast, energy-adjusted intake of fructose from fruit juice and SSB was associated with higher IHL in the fully adjusted models (P = 0.019 and P = 0.009). Individuals in the highest tertile of energy-adjusted intake of fructose from fruit juice and SSB had a 1.04-fold (95% CI 0.99; 1.11) and 1.09-fold (95% CI 1.03; 1.16) higher IHL, respectively, in comparison with the lowest tertile in the fully adjusted models. Finally, the association for fructose from fruit juice was stronger in individuals with type 2 diabetes (P for interaction = 0.071). CONCLUSIONS: Fructose from fruit juice and SSB is independently associated with higher IHL. These cross-sectional findings contribute to current knowledge in support of measures to reduce the intake of fructose-containing beverages as a means to prevent nonalcoholic fatty liver disease at the population level.

Association of Retinal Nerve Fiber Layer Thickness, an Index of Neurodegeneration, With Depressive Symptoms Over Time.

Importance: Whether neurodegeneration contributes to the early pathobiology of late-life depression remains incompletely understood. Objective: To investigate whether lower retinal nerve fiber layer (RNFL) thickness, a marker of neurodegeneration, is associated with the incidence of clinically relevant depressive symptoms and depressive symptoms over time. Design, Setting, and Participants: This is a population-based cohort study from the Netherlands (The Maastricht Study) with baseline examination between 2010 and 2020 and median (IQR) follow-up of 5.0 (3.0-6.0) years. Participants were recruited from the general population. Individuals with type 2 diabetes were oversampled by design. Data analysis was performed from September 2020 to January 2021. Exposures: RNFL, an index of neurodegeneration, assessed with optical coherence tomography. Main Outcomes and Measures: Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ)-9 (continuous score, 0-27) at baseline and over time via annual assessments. The presence of clinically relevant depressive symptoms was defined as a PHQ-9 score of 10 or higher. Results: We used data from 4934 participants with depressive symptoms over time (mean [SD] age, 59.7 [8.4] years; 2159 women [50.8%]; 870 had type 2 diabetes [20.5%]). Lower RNFL thickness was associated with higher incidence of clinically relevant depressive symptoms (per 1 SD, hazard ratio 1.11; 95% CI, 1.01-1.23) and more depressive symptoms over time (per 1 SD, rate ratio, 1.04; 95% CI, 1.01-1.06), after adjustment for demographic, cardiovascular, and lifestyle factors. Conclusions and Relevance: The findings of this study suggest that lower RNFL thickness is associated with higher incidence of clinically relevant depressive symptoms and more depressive symptoms over time. Hence, neurodegeneration may be associated with the early pathobiology of late-life depression.

Organic food use, meat intake, and prevalence of gestational diabetes: KOALA birth cohort study.

PURPOSE: To evaluate whether consumption of organic food and reduced intake of meat products in pregnancy are associated with lower prevalence of gestational diabetes (GD). METHODS: Women participating in the KOALA Birth Cohort Study with valid informed consent, a singleton pregnancy and information on their food intake were considered in this cross-sectional analysis. Participants with and without GD were compared with each other in terms of dietary characteristics (n = 37 and n = 2766, respectively). Multivariable logistic regression (LR) was used to adjust for relevant covariates. RESULTS: Organic food consumption tended to be lower, although not significantly, in women with GD compared to women without GD, whereas consumption of meat was positively associated with GD prevalence. LR modelling showed that GD was significantly associated with higher consumption of meat and, in addition, also of cheese, after adjustment for other relevant covariates. GD was associated with some indicators of animal product intake, namely dietary animal to plant protein ratio and maternal plasma arachidonic acid (for the latter, data available for n = 16 and n = 1304, respectively). Food patterns of participants with GD were characterised by more meat products and less vegetarian products. CONCLUSIONS: Due to the low number of participants with GD, results have to be interpreted cautiously. Consumption of organic food during pregnancy does not seem to be markedly associated with a lower GD prevalence; lower intake of meat and cheese, irrespective of its origin (organic or conventional), does. The latter supports previous studies suggesting a causal association between consumption of animal products and GD.

Carotid stiffness is associated with retinal microvascular dysfunction-The Maastricht study.

OBJECTIVE: This study investigated whether arterial stiffening is a determinant of subtle retinal microvascular changes that precede diabetic retinopathy. RESEARCH DESIGN AND METHODS: This study used cross-sectional data from the Maastricht Study, a type 2 diabetes-enriched population-based cohort study. We used multivariable linear regression analysis to investigate, in individuals without and with type 2 diabetes, the associations of carotid distensibility coefficient and carotid-femoral pulse wave velocity with retinal microvascular diameters and flicker light-induced dilation and adjusted for cardiovascular and lifestyle risk factors. RESULTS: The retinal microvascular diameter study population consisted of N = 2434 participants (51.4% men, mean ± SD age 59.8 ± 8.1 years, and 28.1% type 2 diabetes). No measures of arterial stiffness were significantly associated with microvascular diameters. Greater carotid distensibility coefficient (i.e., lower carotid stiffness) was significantly associated with greater retinal arteriolar flicker light-induced dilation (per standard deviation, standardized beta [95% CI] 0.06 [0.00; 0.12]) and non-significantly, but directionally similarly, associated with greater retinal venular flicker light-induced dilation (0.04 [-0.02; 0.10]). Carotid-femoral pulse wave velocity (i.e., aortic stiffness) was not associated with retinal microvascular flicker light-induced dilation. The associations between carotid distensibility coefficient and retinal arteriolar and venular flicker light-induced dilation were two- to threefold stronger in individuals with type 2 diabetes than in those without. CONCLUSION: In this population-based study greater carotid, but not aortic, stiffness was associated with worse retinal flicker light-induced dilation and this association was stronger in individuals with type 2 diabetes. Hence, carotid stiffness may be a determinant of retinal microvascular dysfunction.

Spousal concordance in pathophysiological markers and risk factors for type 2 diabetes: a cross-sectional analysis of The Maastricht Study.

INTRODUCTION: We compared the degree of spousal concordance in a set of detailed pathophysiological markers and risk factors for type 2 diabetes to understand where in the causal cascade spousal similarities are most relevant. RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of couples who participated in The Maastricht Study (n=172). We used quantile regression models to assess spousal concordance in risk factors for type 2 diabetes, including four adiposity measures, two dimensions of physical activity, sedentary time and two diet indicators. We additionally assessed beta cell function and insulin sensitivity and glucose metabolism status with fasting and 2-hour plasma glucose and hemoglobin A1c. RESULTS: The strongest spousal concordance (beta estimates) was observed for the Dutch Healthy Diet Index (DHDI) in men. A one-unit increase in wives' DHDI was associated with a 0.53 (95% CI 0.22 to 0.67) unit difference in men's DHDI. In women, the strongest concordance was for the time spent in high-intensity physical activity (HPA); thus, a one-unit increase in husbands' time spent in HPA was associated with a 0.36 (95% CI 0.17 to 0.64) unit difference in women's time spent in HPA. The weakest spousal concordance was observed in beta cell function indices. CONCLUSIONS: Spousal concordance was strongest in behavioral risk factors. Concordance weakened when moving downstream in the causal cascade leading to type 2 diabetes. Public health prevention strategies to mitigate diabetes risk may benefit from targeting spousal similarities in health-related behaviors and diabetes risk factors to design innovative and potentially more effective couple-based interventions.

Accelerometer-derived sedentary time and physical activity and the incidence of depressive symptoms - The Maastricht Study.

BACKGROUND: This study examined the associations between accelerometer-derived sedentary time (ST), lower intensity physical activity (LPA), higher intensity physical activity (HPA) and the incidence of depressive symptoms over 4 years of follow-up. METHODS: We included 2082 participants from The Maastricht Study (mean ± s.d. age 60.1 ± 8.0 years; 51.2% men) without depressive symptoms at baseline. ST, LPA and HPA were measured with the ActivPAL3 activity monitor. Depressive symptoms were measured annually over 4 years of follow-up with the 9-item Patient Health Questionnaire (PHQ-9). Cox regression analysis was performed to examine the associations between ST, LPA, HPA and incident depressive symptoms (PHQ-9 ⩾ 10). Analyses were adjusted for total waking time per day, age, sex, education level, type 2 diabetes mellitus, body mass index, total energy intake, smoking status and alcohol use. RESULTS: During 7812.81 person-years of follow-up, 203 (9.8%) participants developed incident depressive symptoms. No significant associations [Hazard Ratio (95% confidence interval)] were found between sex-specific tertiles of ST (lowest v. highest tertile) [1.13 (0.76-1.66], or HPA (highest v. lowest tertile) [1.14 (0.78-1.69)] and incident depressive symptoms. LPA (highest v. lowest tertile) was statistically significantly associated with incident depressive symptoms in women [1.98 (1.19-3.29)], but not in men (p-interaction <0.01). CONCLUSIONS: We did not observe an association between ST or HPA and incident depressive symptoms. Lower levels of daily LPA were associated with an increased risk of incident depressive symptoms in women. Future research is needed to investigate accelerometer-derived measured physical activity and ST with incident depressive symptoms, preferably stratified by sex.

Association of the Amount and Pattern of Physical Activity With Arterial Stiffness: The Maastricht Study.

Background Arterial stiffness is an independent risk factor for cardiovascular disease and can be beneficially influenced by physical activity. However, it is not clear how an individual's physical activity pattern over a week is associated with arterial stiffness. Therefore, we examined the associations of the amount and pattern of higher intensity physical activity with arterial stiffness. Methods and Results Data from the Maastricht Study (n=1699; mean age: 60±8 years, 49.4% women, 26.9% type 2 diabetes mellitus) were used. Arterial stiffness was assessed by carotid-to-femoral pulse wave velocity and carotid distensibility. The amount (continuous variable as h/wk) and pattern (categorical variable) of higher intensity physical activity were assessed with the activPAL3. Activity groups were: inactive (<75 min/wk), insufficiently active (75-150 min/wk), weekend warrior (>150 min/wk in ≤2 sessions), and regularly active (>150 min/wk in ≥3 sessions). In the fully adjusted model (adjusted for demographic, lifestyle, and cardiovascular risk factors), higher intensity physical activity was associated with lower carotid-to-femoral pulse wave velocity (amount: ß = -0.05, 95% CI, -0.09 to -0.01; insufficiently active: ß = -0.33, 95% CI, -0.55 to -0.11; weekend warrior: ß = -0.38, 95% CI, -0.64 to -0.12; and regularly active: ß = -0.46, 95% CI, -0.71 to -0.21 [reference: inactive]). These associations were stronger in those with type 2 diabetes mellitus. There was no statistically significant association between higher intensity physical activity with carotid distensibility. Conclusions Participating in higher intensity physical activity was associated with lower carotid-to-femoral pulse wave velocity, but there was no difference between the regularly actives and the weekend warriors. From the perspective of arterial stiffness, engaging higher intensity physical activity, regardless of the weekly pattern, may be an important strategy to reduce the risk of cardiovascular disease, particularly in individuals with type 2 diabetes mellitus.

Blood pressure variability and microvascular dysfunction: the Maastricht Study.

BACKGROUND: Microvascular dysfunction (MVD) contributes to stroke, dementia, depression, retinopathy and chronic kidney disease. However, the determinants of MVD are incompletely understood. Greater blood pressure variability (BPV) may be one such determinant. METHODS AND RESULTS: We used cross-sectional data of The Maastricht Study (n = 2773, age 59.9 years; 51.9% men) to investigate whether greater very short- to mid-term BPV is associated with various MVD measures. We standardized and averaged within-visit, 24-h and 7-day BPV into a systolic and a diastolic BPV composite score. MVD measures included a composite score of MRI cerebral small vessel disease (CSVD) features (total brain parenchymal volume, white matter hyperintensity volume, lacunar infarcts and cerebral microbleeds), a composite score of flicker light-induced retinal arteriolar and venular dilation response, albuminuria, heat-induced skin hyperemia and a composite score of plasma biomarkers of MVD (sICAM-1, sVCAM-1, sE-selectin and von Willebrand Factor). We used linear regression adjusted for age, sex, glucose metabolism status, mean 24-h systolic or DBP, cardiovascular risk factors and antihypertensive medication. We found that higher systolic and diastolic BPV composite scores (per SD) were associated with higher albuminuria [higher ratio, 1.04 (95% CI 1.00-1.08) and 1.07 (1.03-1.11), respectively], but not with other measures of MVD tested. CONCLUSION: Greater systolic and diastolic BPV was associated with higher albuminuria, but not with CSVD features, flicker light-induced retinal arteriolar and venular dilation response, heat-induced skin hyperemia and plasma biomarkers of MVD. This suggests that the microvasculature of the kidneys is most vulnerable to the detrimental effects of greater BPV.

Associations of 24-Hour Urinary Sodium and Potassium Excretion with Cardiac Biomarkers: The Maastricht Study.

BACKGROUND: It is a matter of debate whether sodium and potassium intake are associated with heart disease. Further, the mechanisms underlying associations of sodium and potassium intake with cardiac events, if any, are not fully understood. OBJECTIVES: We examined cross-sectional associations of 24-h urinary sodium excretion (UNaE) and potassium excretion (UKE), as estimates of their intakes, with high-sensitivity cardiac troponins T (hs-cTnT) and I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), which are markers of cardiomyocyte injury and cardiac dysfunction. METHODS: We included 2961 participants from the population-based Maastricht Study (mean ± SD age 59.8 ± 8.2 y, 51.9% men), who completed the baseline survey between November 2010 and September 2013. Associations were examined with restricted cubic spline linear regression analyses and ordinary linear regression analyses, adjusted for demographics, lifestyle, and cardiovascular disease (CVD) risk factors. RESULTS: Median [IQR] 24-h UNaE and UKE were 3.7 [2.8-4.7] g/24 h and 3.0 [2.4-3.6] g/24 h, respectively. After adjustment for potential confounders, 24-h UNaE was not associated with hs-cTnT, hs-cTnI, and NT-proBNP concentrations. In contrast, after adjustment for potential confounders, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. For example, as compared with the third/median quintile of 24-h UKE (range: 2.8-3.2 g/24 h), participants in the first quintile (range: 0.5-2.3 g/24 h) had 1.05 (95% CI: 0.99, 1.11) times higher hs-cTnT and 1.14 (95% CI: 1.03, 1.26) times higher NT-proBNP. Associations were similar after further adjustment for estimated glomerular filtration rate, albuminuria, blood pressure, and serum potassium. CONCLUSIONS: Twenty-four-hour UNaE was not associated with the studied cardiac biomarkers. In contrast, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. This finding supports recommendations to increase potassium intake in the general population. In addition, it suggests that cardiac dysfunction and/or cardiomyocyte injury may underlie previously reported associations of lower potassium intake with CVD mortality.

Higher levels of daily physical activity are associated with better skin microvascular function in type 2 diabetes-The Maastricht Study.

OBJECTIVE: Physical activity may provide a means for the prevention of cardiovascular disease via improving microvascular function. Therefore, this study investigated whether physical activity is associated with skin and retinal microvascular function. METHODS: In The Maastricht Study, a population-based cohort study enriched with type 2 diabetes (n = 1298, 47.3% women, aged 60.2 ± 8.1 years, 29.5% type 2 diabetes), we studied whether accelerometer-assessed physical activity and sedentary time associate with skin and retinal microvascular function. Associations were studied by linear regression and adjusted for major cardiovascular risk factors. In addition, we investigated whether associations were stronger in type 2 diabetes. RESULTS: In individuals with type 2 diabetes, total physical activity and higher-intensity physical activity were independently associated with greater heat-induced skin hyperemia (regression coefficients per hour), respectively, 10 (95% CI: 1; 18) and 36 perfusion units (14; 58). In individuals without type 2 diabetes, total physical activity and higher-intensity physical activity were not associated with heat-induced skin hyperemia. No associations with retinal arteriolar %-dilation were identified. CONCLUSION: Higher levels of total and higher-intensity physical activity were associated with greater skin microvascular vasodilation in individuals with, but not in those without, type 2 diabetes.

Evaluating the Validity of a Food Frequency Questionnaire in Comparison with a 7-Day Dietary Record for Measuring Dietary Intake in a Population of Survivors of Colorectal Cancer.

BACKGROUND: Food frequency questionnaires (FFQs) are a commonly used method to assess dietary intake in epidemiological studies. It is important to evaluate the validity of FFQs in the population of interest. OBJECTIVE: To evaluate the validity of an FFQ for measuring dietary intake in survivors of colorectal cancer (CRC), relative to a 7-day dietary record. DESIGN: Dietary intake was assessed 1 year after the end of CRC treatment. Participants first completed a 7-day dietary record and 2 weeks later a 253-item FFQ that measured intake in the preceding month. PARTICIPANTS/SETTING: Data were used from a subsample of participants (n=100) enrolled in an ongoing prospective study (EnCoRe study) in the Netherlands, from 2015 to 2018. MAIN OUTCOME MEASURES: Estimated intakes of total energy, 19 nutrients, and 20 food groups as well as scoring adherence to the dietary recommendations of the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) were compared between both dietary assessment methods. STATISTICAL ANALYSES PERFORMED: Means and standard deviations, Spearman rank correlations corrected for within-person variation and total energy, and κ agreement between quintiles were assessed. RESULTS: The median Spearman correlation corrected for within-person variation for nutrients and total energy was 0.60. Correlations >0.50 were found for 15 of 19 nutrients, with highest agreement for vitamin B-12 (0.74), polysaccharides (0.75), and alcohol (0.91). On average, 73% (range=60% to 84%) of participants were classified into the exact same or adjacent nutrient quintile. The median Spearman correlation corrected for within-person variation for food groups was 0.62. Correlations >0.50 were found for 17 of 20 food groups, with highest agreement for cereals and cereal products (0.96), fish (0.96), and potatoes (0.99). The Spearman correlation between total scores of the WCRF/AICR dietary recommendations was 0.53. CONCLUSIONS: Relative to a 7-day dietary record, the validity of an FFQ for measuring dietary intake among survivors of CRC appeared moderate to good for most nutrients and food groups.

Association of artificially sweetened and sugar-sweetened soft drinks with ß-cell function, insulin sensitivity, and type 2 diabetes: the Maastricht Study.

PURPOSE: Artificially sweetened and sugar-sweetened beverage consumptions have both been reported to be associated with type 2 diabetes mellitus (T2D) risk. The aim of the current study was to investigate the potential underlying associations with dynamic pancreatic ß-cell function (BCF) and insulin sensitivity. METHODS: We evaluated cross-sectional associations in 2240 individuals (mean ± SD age 59.6 ± 8.18, 49.4% male, 21.9% T2D) participating in a diabetes-enriched population-based cohort. Artificially sweetened and sugar-sweetened soft drinks and juice consumption were assessed by a food-frequency questionnaire. Glucose metabolism status, insulin sensitivity, and BCF were measured by a seven-point oral glucose tolerance test. Regression analyses were performed to assess associations of artificially and sugar-sweetened beverage consumption with measures of glucose homeostasis. Associations were adjusted for potential confounders, and additionally with and without total energy intake and BMI, as these variables could be mediators. RESULTS: Moderate consumption of artificially sweetened soft drink was associated with lower ß-cell glucose sensitivity [standardized beta (95% CI), - 0.06 (- 0.11, - 0.02)], total insulin secretion [ß - 0.06 (- 0.10, - 0.02)], and with lower ß-cell rate sensitivity [odds ratio (95% CI), 1.29 (1.03, 1.62)] compared to abstainers. Daily artificially sweetened soft drink consumption was associated with lower ß-cell glucose sensitivity [ß - 0.05 (- 0.09, 0.00)], and total insulin secretion [ß - 0.05 - 0.09, - 0.01)] compared to abstainers. CONCLUSIONS: Moderate and daily consumption of artificially sweetened soft drinks was associated with lower BCF, but not with insulin sensitivity. No evidence was found for associations of sugar-sweetened soft drink and juice consumption with BCF or insulin sensitivity in this middle-aged population. Prospective studies are warranted to further investigate the associations of artificially and sugar-sweetened beverage consumption with non-fasting insulin sensitivity and multiple BCF aspects.

The oral glucose tolerance test-derived incremental glucose peak is associated with greater arterial stiffness and maladaptive arterial remodeling: The Maastricht Study.

BACKGROUND: Daily glucose variability may contribute to vascular complication development irrespective of mean glucose values. The incremental glucose peak (IGP) during an oral glucose tolerance test (OGTT) can be used as a proxy of glucose variability. We investigated the association of IGP with arterial stiffness, arterial remodeling, and microvascular function, independent of HbA1c and other confounders. METHODS: IGP was calculated as the peak minus baseline plasma glucose value during a seven-point OGTT in 2758 participants (age: 60 ± 8 years; 48% women) of The Maastricht Study, an observational population-based cohort. We assessed the cross-sectional associations between IGP and arterial stiffness (carotid-femoral pulse wave velocity [cf-PWV], carotid distensibility coefficient [carDC]), arterial remodeling (carotid intima-media thickness [cIMT]; mean [CWSmean] and pulsatile [CWSpuls] circumferential wall stress), and microvascular function (retinal arteriolar average dilatation; heat-induced skin hyperemia) via multiple linear regression with adjustment for age, sex, HbA1c, cardiovascular risk factors, lifestyle factors, and medication use. RESULTS: Higher IGP was independently associated with higher cf-PWV (regression coefficient [B]: 0.054 m/s [0.020; 0.089]) and with higher CWSmean (B: 0.227 kPa [0.008; 0.446]). IGP was not independently associated with carDC (B: - 0.026 10-3/kPa [- 0.112; 0.060]), cIMT (B: - 2.745 µm [- 5.736; 0.245]), CWSpuls (B: 0.108 kPa [- 0.054; 0.270]), retinal arteriolar average dilatation (B: - 0.022% [- 0.087; 0.043]), or heat-induced skin hyperemia (B: - 1.380% [- 22.273; 19.513]). CONCLUSIONS: IGP was independently associated with aortic stiffness and maladaptive carotid remodeling, but not with carotid stiffness, cIMT, and microvascular function measures. Future studies should investigate whether glucose variability is associated with cardiovascular disease.

Consumption of dairy products in relation to the presence of clinical knee osteoarthritis: The Maastricht Study.

PURPOSE: Observational studies showed inverse associations between milk consumption and knee osteoarthritis (knee OA). There is lack of information on the role of specific dairy product categories. We explored the association between dairy consumption and the presence of knee osteoarthritis in 3010 individuals aged 40-75 years participating in The Maastricht Study. METHODS: The presence of knee OA was defined according to a slightly modified version of the American College of Rheumatology (ACR) clinical classification criteria. Data on dairy consumption were appraised by a 253-item FFQ covering 47 dairy products with categorization on fat content, fermentation or dairy type. Multivariable logistic regression analyses were performed to estimate odd ratios (ORs) and 95% confidence intervals (95%CI), while correcting for relevant factors. RESULTS: 427 (14%) participants were classified as having knee OA. Significant inverse associations were observed between the presence of knee OA and intake of full-fat dairy and Dutch, primarily semi-hard, cheese, with OR for the highest compared to the lowest tertile of intake of 0.68 (95%CI 0.50-0.92) for full-fat dairy, and 0.75 (95%CI 0.56-0.99) for Dutch cheese. No significant associations were found for other dairy product categories. CONCLUSION: In this Dutch population, higher intake of full-fat dairy and Dutch cheese, but not milk, was cross-sectionally associated with the lower presence of knee OA. Prospective studies need to assess the relationship between dairy consumption, and in particular semi-hard cheeses, with incident knee OA.

Intakes of Vitamin B-12 from Dairy Food, Meat, and Fish and Shellfish Are Independently and Positively Associated with Vitamin B-12 Biomarker Status in Pregnant Dutch Women.

Background: The effect of vitamin B-12 from different animal foods on vitamin B-12 biomarker status has not previously been evaluated in pregnant women. Objective: We examined the association of vitamin B-12 intake from dairy, meat, fish (including shellfish), and eggs with circulating concentrations of vitamin B-12 biomarkers and with the presence of vitamin B-12 deficiency in 1266 pregnant women participating in the KOALA Birth Cohort Study. Methods: Blood samples were collected in weeks 34-36 of pregnancy, and vitamin B-12 intake from foods and supplements was estimated with a semiquantitative food-frequency questionnaire (FFQ). Total vitamin B-12, holotranscobalamin (holoTC), and methylmalonic acid (MMA) were determined in plasma. Vitamin B-12 deficiency was defined as holoTC <35 pmol/L and MMA >0.45 µmol/L. Associations were evaluated with linear and logistic regression analyses, adjusting for potential confounders. Results: Significant dose-response relations were observed between vitamin B-12 intake from dairy, meat, and fish and plasma vitamin B-12, holoTC, and MMA [P-trend for (shell)fish with MMA = 0.002; P-trend for dairy, meat, and fish with all other markers < 0.001]. The OR (95% CI) of vitamin B-12 deficiency in the third compared with the first tertile of dairy-derived vitamin B-12 was 0.13 (0.04, 0.49), and the ORs for vitamin B-12 from meat and fish were 0.33 (0.11, 0.97) and 0.25 (0.08, 0.82), respectively. Egg-derived vitamin B-12 was only associated with holoTC. Additional analyses showed that self-defined vegetarians and FFQ-defined lacto-ovo-vegetarians had lower median total dietary vitamin B-12 intake and considerably worse vitamin B-12 biomarker status than omnivores and pescatarians. Conclusions: In pregnant Dutch women, higher intakes of vitamin B-12 from dairy, meat, and fish were positively associated with vitamin B-12 status, suggesting that dairy, meat, and fish are good sources of bioactive vitamin B-12 in pregnancy. Nevertheless, for (lacto-)vegetarians, vitamin B-12 supplementation is recommended.

Efficacy of Nutritional Intervention in Elderly After Hip Fracture: A Multicenter Randomized Controlled Trial.

Background: Malnutrition after hip fracture is associated with increased rehabilitation time, complications, and mortality. We assessed the effect of intensive 3 month nutritional intervention in elderly after hip fracture on length of stay (LOS). Methods: Open-label, randomized controlled trial. Exclusion criteria: age < 55 years, bone disease, life expectancy < 1 year, bedridden, using oral nutritional supplements (ONS) before hospitalization, and cognitive impairment. Intervention: weekly dietetic consultation, energy-protein-enriched diet, and ONS (400 mL per day) for 3 months. Control: usual nutritional care. Primary outcome: total LOS in hospital and rehabilitation clinic, including readmissions over 6 months (Cox regression adjusted for confounders); hazard ratio (HR) < 1.0 reflects longer LOS in the intervention group. Secondary outcomes: nutritional and functional status, cognition, quality of life, postoperative complications (6 months); subsequent fractures and all-cause mortality (1 and 5 years). Effect modification by baseline nutritional status was also tested. Results: One hundred fifty-two patients were randomized (73 intervention, 79 control). Median total LOS was 34.0 days (range 4-185 days) in the intervention group versus control 35.5 days (3-183 days; plogrank = .80; adjusted hazard ratio (adjHR): 0.98; 95% CI: 0.68-1.41). Hospital LOS: 12.0 days (4-56 days) versus 11.0 days (3-115 days; p = .19; adjHR: 0.75; 95% CI: 0.53-1.06) and LOS in rehabilitation clinics: 19.5 days (0-174 days) versus 18.5 days (0-168 days; p = .82; adjHR: 1.04; 95% CI: 0.73-1.48). The intervention improved nutritional intake/status at 3, but not at 6 months, and did not affect any other outcome. No difference in intervention effect between malnourished and well-nourished patients was found. Conclusions: Intensive nutritional intervention after hip fracture improved nutritional intake and status, but not LOS or clinical outcomes. Paradigms underlying nutritional intervention in elderly after hip fracture may have to be reconsidered.